English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background  Alveolar capillary dysplasia with or without misalignment of the pulmonary veins (ACD/MPV) is a lethal congenital lung disorder associated with a variety of heterozygous genomic alterations in the  FOXF1  gene or its 60 kb enhancer. Cases without a genomic alteration in the  FOXF1  locus have been described as well. The mechanisms responsible for  FOXF1  haploinsufficiency and the cause of ACD/MPV in patients without a genomic  FOXF1  variant are poorly understood, complicating the search for potential therapeutic targets for ACD/MPV. To investigate the contribution of aberrant DNA methylation, genome wide methylation patterns of ACD/MPV lung tissues were compared with methylation patterns of control lung tissues using the recently developed technique Methylated DNA sequencing (MeD-seq).Results  Eight ACD/MPV lung tissue samples and three control samples were sequenced and their mutual comparison resulted in identification of 319 differentially methylated regions (DMRs) genome wide, involving 115 protein coding genes. The potentially upregulated genes were significantly enriched in developmental signalling pathways, whereas potentially downregulated genes were mainly enriched in O-linked glycosylation. In patients with a large maternal deletion encompassing the 60 kb  FOXF1  enhancer, DNA methylation patterns in this  FOXF1  enhancer were not significantly different compared to controls. However, two hypermethylated regions were detected in the 60 kb  FOXF1  enhancer of patients harbouring a  FOXF1  point mutation. Lastly, a large hypermethylated region overlapping the first  FOXF1  exon was found in one of the ACD/MPV patients without a known pathogenic  FOXF1  variation.Conclusion  This is the first study providing genome wide methylation data on lung tissue of ACD/MPV patients. DNA methylation analyses in the  FOXF1  locus excludes maternal imprinting of the 60 kb  FOXF1  enhancer. Hypermethylation at the 60 kb  FOXF1  enhancer might contribute to  FOXF1  haploinsufficiency caused by heterozygous mutations in the  FOXF1  coding region. Interestingly, DNA methylation analyses of patients without a genomic  FOXF1  variant suggest that abnormal hypermethylation of exon 1 might play a role in some ACD/MPV in patients.    Supplementary Information  The online version contains supplementary material available at 10.1186/s13148-021-01134-1.

clinical epigenetics

Genome wide DNA methylation analysis of alveolar capillary dysplasia lung tissue reveals aberrant methylation of genes involved in development including the FOXF1 locus